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1دورية أكاديمية
المؤلفون: Eleni Petra, Tianlin He, Vasiliki Lygirou, Agnieszka Latosinska, Harald Mischak, Antonia Vlahou, Joachim Jankowski
المصدر: Scientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
الوصف: Abstract The cardiorenal syndrome (CRS) is defined as the confluence of heart-kidney dysfunction. This study investigates the molecular differences at the level of the urinary peptidome between CRS patients and controls and their association to disease pathophysiology. The urinary peptidome of CRS patients (n = 353) was matched for age and sex with controls (n = 356) at a 1:1 ratio. Changes in the CRS peptidome versus controls were identified after applying the Mann–Whitney test, followed by correction for multiple testing. Proteasix tool was applied to investigate predicted proteases involved in CRS-associated peptide generation. Overall, 559 differentially excreted urinary peptides were associated with CRS patients. Of these, 193 peptides were specifically found in CRS when comparing with heart failure and chronic kidney disease urinary peptide profiles. Proteasix predicted 18 proteases involved in > 1% of proteolytic cleavage events including multiple forms of MMPs, proprotein convertases, cathepsins and kallikrein 4. Forty-four percent of the cleavage events were produced by 3 proteases including MMP13, MMP9 and MMP2. Pathway enrichment analysis supported that ECM-related pathways, fibrosis and inflammation were represented. Collectively, our study describes the changes in urinary peptides of CRS patients and potential proteases involved in their generation, laying the basis for further validation.
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/2045-2322Test
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2دورية أكاديمية
المؤلفون: Eleni Petra, Justyna Siwy, Antonia Vlahou, Joachim Jankowski
المصدر: PLoS ONE, Vol 17, Iss 1 (2022)
الوصف: Chronic kidney disease (CKD) is characterized by the loss of kidney function. The molecular mechanisms underlying the development and progression of CKD are still not fully understood. Among others, the urinary peptidome has been extensively studied, with several urinary peptides effectively detecting disease progression. However, their link to proteolytic events has not been made yet. This study aimed to predict the proteases involved in the generation of CKD-associated urinary excreted peptides in a well-matched (for age, sex, lack of heart disease) case-control study. The urinary peptide profiles from CKD (n = 241) and controls (n = 240) were compared and statistically analyzed. The in-silico analysis of the involved proteases was performed using Proteasix and proteases activity was predicted based on the abundance changes of the associated peptides. Predictions were cross-correlated to transcriptomics datasets by using the Nephroseq database. Information on the respective protease inhibitors was also retrieved from the MEROPS database. Totally, 303 urinary peptides were significantly associated with CKD. Among the most frequently observed were fragments of collagen types I, II and III, uromodulin, albumin and beta-2-microglobulin. Proteasix predicted 16 proteases involved in their generation. Through investigating CKD-associated transcriptomics datasets, several proteases are highlighted including members of matrix metalloproteinases (MMP7, MMP14) and serine proteases (PCSK5); laying the foundation for further studies towards elucidating their role in CKD pathophysiology.
وصف الملف: electronic resource
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3دورية أكاديمية
المؤلفون: Debbie McLaggan, Maria R Amezaga, Eleni Petra, Andrew Frost, Elizabeth I Duff, Stewart M Rhind, Paul A Fowler, L Anne Glover, Cristina Lagido
المصدر: PLoS ONE, Vol 7, Iss 10, p e46503 (2012)
الوصف: A transgenic strain of the model nematode Caenorhabditis elegans in which bioluminescence reports on relative, whole-organism ATP levels was used to test an environmentally-relevant mixture of pollutants extracted from processed sewage sludge. Changes in bioluminescence, following exposure to sewage sludge extract, were used to assess relative ATP levels and overall metabolic health. Reproductive function and longevity were also monitored. A short (up to 8 h) sublethal exposure of L4 larval stage worms to sewage sludge extract had a concentration-dependent, detrimental effect on energy status, with bioluminescence decreasing to 50-60% of the solvent control (1% DMSO). Following longer exposure (22-24 h), the energy status of the nematodes showed recovery as assessed by bioluminescence. Continuous exposure to sewage sludge extract from the L4 stage resulted in a shorter median lifespan relative to that of solvent or medium control animals, but only in the presence of 400-600 µM 5-fluoro-2'-deoxyuridine (FUdR), which was incorporated to inhibit reproduction. This indicated that FUdR increased lifespan, and that the effect was counteracted by SSE. Exposure to sewage sludge extract from the L1 stage led to slower growth and a delayed onset of egg laying. When L1 exposed nematodes reached the reproductive stage, no effect on egg laying rate or egg number in the uterus was observed. DMSO itself (1%) had a significant inhibitory effect on growth and development of C. elegans exposed from the L1 stage and on reproduction when exposed from the L4 stage. Results demonstrate subtle adverse effects on C. elegans of a complex mixture of environmental pollutants that are present, individually, in very low concentrations and indicate that our biosensor of energy status is a novel, sensitive, rapid, quantitative, whole-organism test system which is suitable for high throughput risk assessment of complex pollutant mixtures.
وصف الملف: electronic resource
العلاقة: http://europepmc.org/articles/PMC3463613?pdf=renderTest; https://doaj.org/toc/1932-6203Test
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4
المؤلفون: Àngel Argilés, Vasiliki Lygirou, Eleni Petra, Flore Duranton, Harald Mischak, Manousos Makridakis, Jerome Zoidakis, Szymon Filip, Antonia Vlahou, Georgia Kontostathi, Rafael Stroggilos
المصدر: Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
Scientific Reportsمصطلحات موضوعية: Male, 0301 basic medicine, Oncology, 030232 urology & nephrology, lcsh:Medicine, Disease, Mass Spectrometry, Cohort Studies, Prognostic markers, 0302 clinical medicine, Multiplex, Longitudinal Studies, lcsh:Science, Aged, 80 and over, Multidisciplinary, Immunoglobulin heavy constant alpha 1, Middle Aged, Prognosis, Blood proteins, Hemoglobin Subunits, Disease Progression, Female, medicine.symptom, Complement C1 Inhibitor Protein, Glomerular Filtration Rate, Adult, medicine.medical_specialty, Quantitative proteomics, Proteomic analysis, Renal function, Article, 03 medical and health sciences, Internal medicine, Alpha-Globulins, medicine, Humans, Renal Insufficiency, Chronic, Aged, business.industry, lcsh:R, medicine.disease, 030104 developmental biology, Albuminuria, Muramidase, lcsh:Q, beta 2-Microglobulin, business, Biomarkers, Follow-Up Studies, Kidney disease
الوصف: Current diagnostic measures for Chronic Kidney Disease (CKD) include detection of reduced estimated glomerular filtration rate (eGFR) and albuminuria, which have suboptimal accuracies in predicting disease progression. The disease complexity and heterogeneity underscore the need for multiplex quantification of different markers. The goal of this study was to determine the association of six previously reported CKD-associated plasma proteins [B2M (Beta-2-microglobulin), SERPINF1 (Pigment epithelium-derived factor), AMBP (Protein AMBP), LYZ (Lysozyme C), HBB (Hemoglobin subunit beta) and IGHA1 (Immunoglobulin heavy constant alpha 1)], as measured in a multiplex format, with kidney function, and outcome. Antibody-free, multiple reaction monitoring mass spectrometry (MRM) assays were developed, characterized for their analytical performance, and used for the analysis of 72 plasma samples from a patient cohort with longitudinal follow-up. The MRM significantly correlated (Rho = 0.5–0.9) with results from respective ELISA. Five proteins [AMBP, B2M, LYZ, HBB and SERPINF1] were significantly associated with eGFR, with the three former also associated with unfavorable outcome. The combination of these markers provided stronger associations with outcome (p
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f45ed4d3b1c70609a58b348a2d897aa9Test
http://link.springer.com/article/10.1038/s41598-020-61496-zTest -
5
المؤلفون: Eleni Petra (129612), Justyna Siwy (103595), Antonia Vlahou (114470), Joachim Jankowski (114466)
مصطلحات موضوعية: Biochemistry, Medicine, Microbiology, Genetics, Molecular Biology, Physiology, Sociology, Marine Biology, Cancer, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Mathematical Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, studies towards elucidating, respective protease inhibitors, molecular mechanisms underlying, matrix metalloproteinases (<, highlighted including members, urinary peptide profiles, serine proteases (<, 303 urinary peptides, performed using proteasix, div >< p, chronic kidney disease, associated transcriptomics datasets, transcriptomics datasets, associated peptides, urinary peptidome, kidney function, heart disease
الوصف: (XLSX)
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6
المؤلفون: Eleni Petra (129612), Justyna Siwy (103595), Antonia Vlahou (114470), Joachim Jankowski (114466)
مصطلحات موضوعية: Biochemistry, Medicine, Microbiology, Genetics, Molecular Biology, Physiology, Sociology, Marine Biology, Cancer, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Mathematical Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, studies towards elucidating, respective protease inhibitors, molecular mechanisms underlying, matrix metalloproteinases (<, highlighted including members, urinary peptide profiles, serine proteases (<, 303 urinary peptides, performed using proteasix, div >< p, chronic kidney disease, associated transcriptomics datasets, transcriptomics datasets, associated peptides, urinary peptidome, kidney function, heart disease
الوصف: (XLSX)
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7
المؤلفون: Eleni Petra (129612), Justyna Siwy (103595), Antonia Vlahou (114470), Joachim Jankowski (114466)
مصطلحات موضوعية: Biochemistry, Medicine, Microbiology, Genetics, Molecular Biology, Physiology, Sociology, Marine Biology, Cancer, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Mathematical Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, studies towards elucidating, respective protease inhibitors, molecular mechanisms underlying, matrix metalloproteinases (<, highlighted including members, urinary peptide profiles, serine proteases (<, 303 urinary peptides, performed using proteasix, div >< p, chronic kidney disease, associated transcriptomics datasets, transcriptomics datasets, associated peptides, urinary peptidome, kidney function, heart disease
الوصف: (XLSX)
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8صورة
المؤلفون: Eleni Petra (129612), Justyna Siwy (103595), Antonia Vlahou (114470), Joachim Jankowski (114466)
مصطلحات موضوعية: Biochemistry, Medicine, Microbiology, Genetics, Molecular Biology, Physiology, Sociology, Marine Biology, Cancer, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Mathematical Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, studies towards elucidating, respective protease inhibitors, molecular mechanisms underlying, matrix metalloproteinases (<, highlighted including members, urinary peptide profiles, serine proteases (<, 303 urinary peptides, performed using proteasix, div >< p, chronic kidney disease, associated transcriptomics datasets, transcriptomics datasets, associated peptides, urinary peptidome, kidney function, heart disease
الوصف: ( A ) Volcano plot showing the fold change (log 2 CKD/non-CKD) plotted against the BH p-value (-log 10 ) of the 303 differentially excreted CKD-associated peptides. The top five most increased and decreased abundance peptides in CKD patients are highlighted in blue (for increased) and red (for decreased) colours. ( B ) Heatmap of the log 2 transformed fold change of the top 10 most increased and decreased peptides in CKD patients. In each case, the peptide codes are provided in the S1 Table . ( C ) Pie chart of the top 15 most frequently observed protein precursors, that covered 76% (n = 230) of differentially excreted CKD-associated peptides. The percentage of the differentially excreted peptides per protein precursor is presented.
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9صورة
المؤلفون: Eleni Petra (129612), Justyna Siwy (103595), Antonia Vlahou (114470), Joachim Jankowski (114466)
مصطلحات موضوعية: Biochemistry, Medicine, Microbiology, Genetics, Molecular Biology, Physiology, Sociology, Marine Biology, Cancer, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Mathematical Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, studies towards elucidating, respective protease inhibitors, molecular mechanisms underlying, matrix metalloproteinases (<, highlighted including members, urinary peptide profiles, serine proteases (<, 303 urinary peptides, performed using proteasix, div >< p, chronic kidney disease, associated transcriptomics datasets, transcriptomics datasets, associated peptides, urinary peptidome, kidney function, heart disease
الوصف: ( A ) The 24 predicted proteases which possibly involved in the endogenous cleavage of the CKD-associated peptides are presented. Of these 24, 16 proteases had > 1% of cleavage events and are highlighted in red and green colours. Eleven metalloproteinases (highlighted in red) and 5 serine proteases (highlighted in green) are presented. ( B ) Heatmap of the log 2 transformed abundance of the differentially excreted peptides grouped based on the predicted proteases. These peptides were used as substrates by the 16 shortlisted proteases. ( C ) Heatmap of the shortlisted proteases with their calculated activity score. The activated proteases are highlighted in red whereas the deactivated proteases are highlighted in green.
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10صورة
المؤلفون: Eleni Petra (129612), Justyna Siwy (103595), Antonia Vlahou (114470), Joachim Jankowski (114466)
مصطلحات موضوعية: Biochemistry, Medicine, Microbiology, Genetics, Molecular Biology, Physiology, Sociology, Marine Biology, Cancer, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Mathematical Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, studies towards elucidating, respective protease inhibitors, molecular mechanisms underlying, matrix metalloproteinases (<, highlighted including members, urinary peptide profiles, serine proteases (<, 303 urinary peptides, performed using proteasix, div >< p, chronic kidney disease, associated transcriptomics datasets, transcriptomics datasets, associated peptides, urinary peptidome, kidney function, heart disease
الوصف: Pathway enrichment analysis of the 16 shortlisted proteases along with the 69 protein precursors of the differentially excreted peptides was performed by the Reactome pathway database. The 10 most significant clusters are presented in different colours and the most significant term of each cluster is selected as a label. The associated proteases are highlighted in red colour.
النص الكامل